Assessment of mechanism of acquired skewed X inactivation by analysis of twins.

Abstract:

:Skewed X-chromosome inactivation in peripheral blood granulocytes becomes more frequent with increasing age, affecting up to half of those over 75 years old. To investigate the mechanisms underlying this phenomenon, X-inactivation profiles in 33 monozygotic and 22 dizygotic elderly twin pairs were studied. Differential methylation-sensitive restriction enzyme cutting at a hypervariable locus in the human androgen receptor gene (HUMARA) was studied on purified granulocytes using T cells as controls. A large genetic effect on skewed granulocytic X inactivation was shown (P <.05); heritability was estimated to be 0.68. A minor part (SD.0151 relative allele frequency [ie, larger/smaller] units) of the observed variance is due to experimental error. A further contributor to acquired skewing is stochastic asymmetric stem cell division, which was modeled and shown as unlikely to account for a substantial part of variance. Two monozygotic twin pairs had X-inactivation ratios skewed markedly in opposite directions, evidence for a further stochastic mechanism, suggestive of a single overrepresented clone. In conclusion, all 3 suggested mechanisms contribute to acquired X inactivation but the dominant mechanism is genetic selection. The observed proportion of putatively clonal hematopoiesis is similar to the lifetime incidence of hematopoietic stem cell malignancy consistent with the concept that clonal hematopoiesis precedes stem cell malignancy.

journal_name

Blood

journal_title

Blood

authors

Vickers MA,McLeod E,Spector TD,Wilson IJ

doi

10.1182/blood.v97.5.1274

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

1274-81

issue

5

eissn

0006-4971

issn

1528-0020

journal_volume

97

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein.

    abstract::The most common chromosomal abnormality of infant acute lymphoblastic leukemia (ALL) is the t(4;11)(q21;q23) that gives rise to the MLL/AF4 fusion gene. Leukemic blasts expressing MLL/AF4 are arrested at an early progenitor stage with lymphoid or monocytoid characteristics. A novel B-lineage ALL cell line termed B-lin...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.12.3398

    authors: Bertrand FE,Vogtenhuber C,Shah N,LeBien TW

    更新日期:2001-12-01 00:00:00

  • Podoplanin-positive periarteriolar stromal cells promote megakaryocyte growth and proplatelet formation in mice by CLEC-2.

    abstract::Megakaryopoiesis is the hierarchical differentiation of hematopoietic stem cells into megakaryocytes. Differentiating megakaryocytes undergo maturation characterized by endomitosis and produce numerous platelets through proplatelet formation. C-type lectin-like receptor 2 (CLEC-2) is a podoplanin (PDPN) receptor mainl...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-08-663708

    authors: Tamura S,Suzuki-Inoue K,Tsukiji N,Shirai T,Sasaki T,Osada M,Satoh K,Ozaki Y

    更新日期:2016-03-31 00:00:00

  • Survivin regulates hematopoietic progenitor cell proliferation through p21WAF1/Cip1-dependent and -independent pathways.

    abstract::The cyclin-dependent kinase inhibitor p21WAF1/Cip1 and Survivin enhance granulocyte macrophage colony-forming unit (CFU-GM) cell cycle and proliferation and have been implicated as antiapoptotic proteins. We investigated the relationships between p21 and Survivin in primary CFU-GM and c-kit+, lineage-negative (Lin-) c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-05-1756

    authors: Fukuda S,Mantel CR,Pelus LM

    更新日期:2004-01-01 00:00:00

  • MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients.

    abstract::Measurements of hepatic iron concentration (HIC) are important predictors of transfusional iron burden and long-term outcome in patients with transfusion-dependent anemias. The goal of this work was to develop a readily available, noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2) and R2* ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-10-3982

    authors: Wood JC,Enriquez C,Ghugre N,Tyzka JM,Carson S,Nelson MD,Coates TD

    更新日期:2005-08-15 00:00:00

  • Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation.

    abstract::Epigenetic events that are essential drivers of lymphocyte transformation remain incompletely characterized. We used models of Epstein-Barr virus (EBV)-induced B-cell transformation to document the relevance of protein arginine methyltransferase 5 (PRMT5) to regulation of epigenetic-repressive marks during lymphomagen...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-12-619783

    authors: Alinari L,Mahasenan KV,Yan F,Karkhanis V,Chung JH,Smith EM,Quinion C,Smith PL,Kim L,Patton JT,Lapalombella R,Yu B,Wu Y,Roy S,De Leo A,Pileri S,Agostinelli C,Ayers L,Bradner JE,Chen-Kiang S,Elemento O,Motiwala T

    更新日期:2015-04-16 00:00:00

  • A randomized prospective comparison of chemotherapy to total body irradiation as initial treatment for the indolent lymphoproliferative diseases.

    abstract::One hundred eight consecutive patients with indolent lymphoproliferative diseases were stratified into chronic lymphocytic leukemia (CLL), stage III and IV well-differentiated lymphocytic lymphoma (WDLL), and stage III and IV follicular lymphoma (FL). Within each stratum, patients were prospectively and randomly assig...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Jacobs P,King HS

    更新日期:1987-06-01 00:00:00

  • Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes.

    abstract::A cohort of MDS patients was examined for mutations affecting 4 splice genes (SF3B1, SRSF2, ZRSR2, and U2AF35) and evaluated in the context of clinical and molecular markers. Splice gene mutations were detected in 95 of 221 patients. These mutations were mutually exclusive and less likely to occur in patients with com...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-12-400994

    authors: Damm F,Kosmider O,Gelsi-Boyer V,Renneville A,Carbuccia N,Hidalgo-Curtis C,Della Valle V,Couronné L,Scourzic L,Chesnais V,Guerci-Bresler A,Slama B,Beyne-Rauzy O,Schmidt-Tanguy A,Stamatoullas-Bastard A,Dreyfus F,Prébet T,

    更新日期:2012-04-05 00:00:00

  • Identification of CD8alpha+CD11c- lineage phenotype-negative cells in the spleen as committed precursor of CD8alpha+ dendritic cells.

    abstract::CD8alpha+ dendritic cells (DCs) represent a functionally distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of CD8alpha+ DCs remains to be identified. We reported here that murine splenic CD8alpha+CD11c- lineage phenotype (Lin)- cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v100.2.569

    authors: Wang Y,Zhang Y,Yoneyama H,Onai N,Sato T,Matsushima K

    更新日期:2002-07-15 00:00:00

  • Structural and functional implications of the intron/exon organization of the human endothelial cell protein C/activated protein C receptor (EPCR) gene: comparison with the structure of CD1/major histocompatibility complex alpha1 and alpha2 domains.

    abstract::The endothelial cell protein C/activated protein C receptor (EPCR) is located primarily on the surface of the large vessels of the vasculature. In vitro studies suggest that it is involved in the protein C anticoagulant pathway. We report the organization and nucleotide sequence of the human EPCR gene. It spans approx...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Simmonds RE,Lane DA

    更新日期:1999-07-15 00:00:00

  • There's no such fool like an immunosenescent fool.

    abstract::In this issue of Blood, Stepensky et al provide an astute description of immunosenescence arising from deficiency in tripeptidyl peptidase II (TPPII). Senescence of T and B lymphocytes is a striking finding, which has recently come into the limelight because it can be linked to primary immunodeficiency syndromes with ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2014-12-614149

    authors: Seidel MG

    更新日期:2015-01-29 00:00:00

  • Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression.

    abstract::We previously reported that RO(+) expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD(-)CD38(+) GC B cells, into different fractions based on RB expression. Although each subset contained RB(+) cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-03-145979

    authors: Jackson SM,Harp N,Patel D,Wulf J,Spaeth ED,Dike UK,James JA,Capra JD

    更新日期:2009-04-23 00:00:00

  • High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine.

    abstract::Although virtually all pediatric patients with acute myeloid leukemia (AML) achieve a complete remission after initial induction therapy, 30%-40% of patients will encounter a relapse and have a dismal prognosis. To prevent relapses, personalized treatment strategies are currently being developed, which target specific...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-03-276519

    authors: Bachas C,Schuurhuis GJ,Hollink IH,Kwidama ZJ,Goemans BF,Zwaan CM,van den Heuvel-Eibrink MM,de Bont ES,Reinhardt D,Creutzig U,de Haas V,Assaraf YG,Kaspers GJ,Cloos J

    更新日期:2010-10-14 00:00:00

  • Cell-surface heparan sulfate proteoglycan-mediated regulation of human neutrophil migration by the serpin antithrombin III.

    abstract::The serpin antithrombin III (AT III) is reported to have hemostasis-regulating and anti-inflammatory properties. To determine its ability to influence thrombin-independent leukocyte responses, the direct effects of the AT III concentrate Kybernin P and a monoclonal antibody-purified AT III on neutrophil migration were...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.4.1079

    authors: Dunzendorfer S,Kaneider N,Rabensteiner A,Meierhofer C,Reinisch C,Römisch J,Wiedermann CJ

    更新日期:2001-02-15 00:00:00

  • Lentiviral gene transfer into peripheral blood-derived CD34+ NOD/SCID-repopulating cells.

    abstract::This study reports a lentiviral gene transfer protocol for efficient transduction of adult human peripheral blood (PB)-derived CD34+ NOD/SCID-repopulating cells (SRCs) using vesicular stomatitis virus-G protein (VSV-G)-pseudotyped lentiviruses encoding for enhanced green fluorescence protein (eGFP). Lentiviral stocks ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.2.709

    authors: Scherr M,Battmer K,Blömer U,Schiedlmeier B,Ganser A,Grez M,Eder M

    更新日期:2002-01-15 00:00:00

  • Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation.

    abstract::Interleukin-25 (IL-25) is a recently described T helper 2 (T(H)2) cell-derived cytokine that belongs to the IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non-T-cell population. Here, we show that mast cells are also potent IL-25-producing cells. When bone marrow-derived mast cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-09-2817

    authors: Ikeda K,Nakajima H,Suzuki K,Kagami S,Hirose K,Suto A,Saito Y,Iwamoto I

    更新日期:2003-05-01 00:00:00

  • Independent formation of DnaseI hypersensitive sites in the murine beta-globin locus control region.

    abstract::Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HS...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bender MA,Mehaffey MG,Telling A,Hug B,Ley TJ,Groudine M,Fiering S

    更新日期:2000-06-01 00:00:00

  • Bone loss caused by iron overload in a murine model: importance of oxidative stress.

    abstract::Osteoporosis is a frequent problem in disorders characterized by iron overload, such as the thalassemias and hereditary hemochromatosis. The exact role of iron in the development of osteoporosis in these disorders is not established. To define the effect of iron excess in bone, we generated an iron-overloaded mouse by...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-12-260083

    authors: Tsay J,Yang Z,Ross FP,Cunningham-Rundles S,Lin H,Coleman R,Mayer-Kuckuk P,Doty SB,Grady RW,Giardina PJ,Boskey AL,Vogiatzi MG

    更新日期:2010-10-07 00:00:00

  • Defective polymorphonuclear leukocyte metabolism and function in canine cyclic neutropenia.

    abstract::Humans and grey collie dogs with cyclic neutropenia are known to suffer from an increased rate of bacterial infection. Because of the previously described microanatomic abnormalities of lysosome formation found in the polymorphonuclear leukocytes (PMNs) of dogs with canine cyclic neutropenia, studies of these cells we...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chusid MJ,Bujak JS,Dale DC

    更新日期:1975-12-01 00:00:00

  • Acquired granular pool defect in stored platelets.

    abstract::Platelets stored as concentrates (PC) for 72 h at 22 degrees C develop a functional defect. Alterations in adenine nucleotides of platelets have been shown to affect platelet function. Adenine nucleotide content of platelets was measured before and after storage and a decrease of 27.1 /+- 1.7% (mean /+- SE) in ATP and...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rao AK,Niewiarowski S,Murphy S

    更新日期:1981-02-01 00:00:00

  • Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men.

    abstract::We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on cytokine and cytokine receptor plasma levels and on the in vivo host response to Salmonella abortus equi endotoxin in healthy males. Twenty volunteers received 0.8 ng/kg endotoxin and saline intravenously 1 week apart in randomized order. ...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Pollmächer T,Korth C,Mullington J,Schreiber W,Sauer J,Vedder H,Galanos C,Holsboer F

    更新日期:1996-02-01 00:00:00

  • How I treat chronic graft-versus-host disease.

    abstract::Allogeneic stem cell transplantation (SCT) is now a commonplace procedure. Clinicians who care for patients with hematologic malignancies and aplastic anemia are almost certain to follow up patients after SCT. This review is intended to help clinicians observe patients for probably the most important late complication...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood.v97.5.1196

    authors: Vogelsang GB

    更新日期:2001-03-01 00:00:00

  • Tuning the volume of the immune response: strength and persistence of stimulation determine migration and cytokine secretion of dendritic cells.

    abstract::Migration to lymph nodes and secretion of cytokines are critical functions of mature dendritic cells (DCs); however, these 2 functions are not necessarily linked. This is the first report showing that quantitative differences in identical signaling pathways determine DC migration and cytokine secretion. Using differen...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-12-4146

    authors: Luft T,Maraskovsky E,Schnurr M,Knebel K,Kirsch M,Görner M,Skoda R,Ho AD,Nawroth P,Bierhaus A

    更新日期:2004-08-15 00:00:00

  • Suppression of mouse myelopoiesis by administration of human lactoferrin in vivo and the comparative action of human transferrin.

    abstract::Purified human lactoferrin was assessed for its influence in vivo in untreated mice and in mice undergoing rebound myelopoiesis after sublethal dosages of Cytoxan. Fully iron-saturated lactoferrin suppressed the numbers of granulocytes and monocytes per femur, the numbers of granulocyte-macrophage progenitor cells (CF...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gentile P,Broxmeyer HE

    更新日期:1983-05-01 00:00:00

  • Transient receptor potential vanilloid 1 mediates pain in mice with severe sickle cell disease.

    abstract::Pain is the leading cause of emergency department visits, hospitalizations, and daily suffering in individuals with sickle cell disease (SCD). The pathologic mechanisms leading to the perception of pain during acute RBC sickling episodes and development of chronic pain remain poorly understood and ineffectively treate...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-327429

    authors: Hillery CA,Kerstein PC,Vilceanu D,Barabas ME,Retherford D,Brandow AM,Wandersee NJ,Stucky CL

    更新日期:2011-09-22 00:00:00

  • EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation.

    abstract::Autologous T cells targeting Epstein-Barr virus (EBV) latent membrane proteins (LMPs) have shown safety and efficacy in the treatment of patients with type 2 latency EBV-associated lymphomas for whom standard therapies have failed, including high-dose chemotherapy followed by autologous stem-cell rescue. However, the ...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2018-07-863654

    authors: McLaughlin LP,Rouce R,Gottschalk S,Torrano V,Carrum G,Wu MF,Hoq F,Grilley B,Marcogliese AM,Hanley PJ,Gee AP,Brenner MK,Rooney CM,Heslop HE,Bollard CM

    更新日期:2018-11-29 00:00:00

  • Somatic hypermutation in low-grade mucosa-associated lymphoid tissue-type B-cell lymphoma.

    abstract::The origin of low-grade mucosa-associated lymphoid tissue (MALT)-type B-cell lymphoma is still unclear. Using a novel two-step procedure, we have sequenced the Ig VH genes expressed by cells from four patients with gastric low-grade MALT-type lymphoma. The nucleotide sequences of the complementarity determining region...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Qin Y,Greiner A,Trunk MJ,Schmausser B,Ott MM,Müller-Hermelink HK

    更新日期:1995-11-01 00:00:00

  • Identification of the dombrock blood group glycoprotein as a polymorphic member of the ADP-ribosyltransferase gene family.

    abstract::Identification of the 25 known human blood group molecules is of fundamental importance for the fields of erythroid cell biology and transfusion medicine. Here we provide the first molecular description of the "Dombrock" blood group system. A candidate gene was identified by in silico analyses of approximately 5000 ex...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gubin AN,Njoroge JM,Wojda U,Pack SD,Rios M,Reid ME,Miller JL

    更新日期:2000-10-01 00:00:00

  • An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1).

    abstract::A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Koeffler HP,Billing R,Lusis AJ,Sparkes R,Golde DW

    更新日期:1980-08-01 00:00:00

  • Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection.

    abstract::Hematopoietic stem and progenitor cells were previously found to express Toll-like receptors (TLRs), suggesting that bacterial/viral products may influence blood cell formation. We now show that common lymphoid progenitors (CLPs) from mice with active HSV-1 infection are biased to dendritic cell (DC) differentiation, ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-04-151506

    authors: Welner RS,Pelayo R,Nagai Y,Garrett KP,Wuest TR,Carr DJ,Borghesi LA,Farrar MA,Kincade PW

    更新日期:2008-11-01 00:00:00

  • Genetic expression of adenosine deaminase in human lymphoid malignancies.

    abstract::Adenosine deaminase (ADA) is an enzyme in the purine catabolic pathway that has been used as an enzymatic marker of T cell lymphoblastic malignancies due to its high specific activity in thymocytes and immature T cells. We have investigated whether the level of ADA activity in lymphoid leukemic cells correlates with t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gan TE,Dadonna PE,Mitchell BS

    更新日期:1987-05-01 00:00:00